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Human genetics implicate thromboembolism in the pathogenesis of long COVID in individuals of European ancestry

Art Schuermans1,2,3, Andreas Verstraete4,5, Vilma Lammi6,7

  • 1KU Leuven Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, Leuven, Belgium. aschuerm@broadinstitute.org.

Nature Cardiovascular Research
|December 16, 2025
PubMed

Insights

Genetic links between blood clots (thromboembolism) and long COVID provide new insights into the condition

Area of Science:

  • Genetics
  • Immunology
  • Infectious Diseases

Background:

  • Long COVID presents with diverse post-acute symptoms affecting multiple organs.
  • Mechanisms for long COVID, such as inflammation and thromboembolism, lack robust human evidence.
  • Causal links between SARS-CoV-2 infection and long COVID pathogenesis remain unclear.

Purpose of the Study:

  • To investigate the association between genetic variants related to thromboembolism and the risk of developing long COVID.
  • To identify potential molecular pathways contributing to long COVID through genetic analysis.

Main Methods:

  • Utilized data from the Long COVID Host Genetics Initiative (3,018 cases, 994,582 controls).
  • Employed Mendelian randomization to assess the causal effect of genetically predicted venous thromboembolism risk on long COVID.
  • Conducted downstream analyses using gene-specific instruments and expression data.

Main Results:

  • Increased genetically predicted venous thromboembolism risk was significantly associated with higher odds of long COVID (OR=1.21).
  • This association remained independent of acute COVID-19 severity and was confirmed in external datasets.
  • Protease-activated receptor 1 (PAR-1) was identified as a potential molecular contributor.

Conclusions:

  • Human genetic evidence supports shared pathogenetic pathways between thromboembolism and long COVID.
  • Findings suggest that thromboembolic processes may play a role in the development of long COVID.
  • Identifies PAR-1 as a potential therapeutic target for long COVID.

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